Fluoride & Secondary Hyperparathyroidism

F.A.N. | May 2012 | By Michael Connett

Among humans with skeletal fluorosis, fluoride may cause secondary hyperparathyroidism or cause bone damage resembling secondary hyperparathyroidism. Secondary hyperparathyroidism is a condition in which the parathyroid glands produce too much parathyroid hormone. The condition, which commonly results from kidney disease, is triggered when the levels of calcium and phosphorous in the blood are too low. In order to ensure a sufficient supply of calcium and phosphous in the blood, the parathyroid hormone (PTH) stimulates bone cells (osteoclasts) to break down the bone. Secondary hyperparathyroidism is a frequent cause of renal osteodystrophy.

Fluoride & Secondary Hyperparathyroidism:

“This study was conducted to find out the possible underlying mechanism of various manifestation of fluorosis, a disease caused by excess ingestion of fluoride. For this the fluoride belt of Jaipur district was selected. The parameters selected were serum Parathyroid hormone, the levels of which are directly affected by fluoride intake. The levels of serum seromucoid, serum and leucocyte ascorbic acid, serum sialic acid (SSA) reflects ground substance metabolism. The study was conducted on two hundred children, selected from four areas (50 from each area) consuming water containing 2.4, 4.6, 5.6 and 13.6 mg/l of fluoride. Drinking water fluoride and serum fluoride were measured by Ion selective electrode method. Serum parathyroid by RIA and all other parameters were measured spectrophotometrically. The results revealed an increase in levels of fluoride, parathyroid hormone and seromucoid in serum with increasing water fluoride concentrations. Serum Calcium and serum ascorbic acid were found in normal range, how ever leucocyte ascorbic acid were decreased. A high positive correlation among fluoride concentration in drinking water and serum parathyroid hormone (r=0.967), and, serum parathyroid hormone and serum seromucoid concentration (r=0.935) was also observed The results indicated that secondary hyperparathyroidism due to hypocalcemic stress caused by excess fluoride ingestion disturbs normal metabolism of ground substance in calcified tissues of the body reflected as altered levels of the components of ground substance in the serum.”
SOURCE: Gupta SK, et al. (2012). Changes in serum seromucoid following compensatory hyperparathyroidism: A sequel to chronic fluoride ingestion. Indian Journal of Clinical Biochemistry 23(2):176-180.

“Fluoride is a cumulative element that increases metabolic turnover of the bone and also affects the homeostasis of bone mineral metabolism. There are number of similarities between the effects of excess parathyroid hormone (PTH) and fluorosis on bone. So fluoride might show its effect via PTH. We aimed to determine PTH levels in patients with endemic fluorosis to estimate the possible toxic effects of chronic fluoride intake. Fifty-six patients withendemic fluorosis and 28 age-, sex-, and body-mass-index-matched healthy controls were included in this study. Endemic fluorosis was diagnosed according to the clinical diagnosis criteria of Wang. The urine fluoride levels of fluorosis patients were significantly higher than those of control subjects as expected (1.9 ± 0.1 vs. 0.4 ± 0.1 mg/L, respectively; P < 0.001). PTH levels in fluorosis group were significantly higher than control group (65.09 ± 32.91 versus 47.40 ± 20.37, respectively; P = 0.01). The results of our study demonstrate that serum PTH levelsare increased in patients with endemic fluorosis. Fluoride, by interfering calcium balance, may be the cause of secondary hyperparathyroidism.”
SOURCE: Koroglu BK, et al. (2011). Serum parathyroid hormone levels in chronic endemic fluorosis. Biol Trace Elem Res. 143(1):79-86.

“OBJECTIVE: To evaluate the effect of varying ingestion of drinking water containing high fluorides and its effect on serum parathyroid hormone. DESIGN: Cross sectional clinical study. SETTING: S.M.S. Medical College, Jaipur. SUBJECT: 200 children were selected from four areas (50 from each area) consuming water containing 2.4, 4.6, 5.6 and 13.5 mg/l of fluoride. All children were in an age group of 6 to 12 years. METHODS: All children were graded for clinical, radiological and dental fluorosis and biochemical estimations were made for serum calcium, serum and urinary fluoride and serum parathyroid hormone. RESULTS: Serum calcium levels were well within normal range in the patients of all areas but an increase in serum parathyroid levels (S. PTH) was noted. The increased S. PTH was well correlated with increase in fluoride ingestion. The severity of clinical and skeletal fluorosis was observed to increase with increase in S. PTH concentration. CONCLUSIONS: High Fluoride ingestion has a definite relationship with increased parathyroid hormone secretion, which may be responsible for maintaining serum calcium levels and may have a role in toxic manifestations of fluorosis.”
SOURCE: Gupta SK, et al. (2001). Compensatory hyperparathyroidism following high fluoride ingestion – a clinico – biochemical correlation. Indian Pediatr. 38(2):139-46.

“The effect of fluoride on osteoclasts is less well understood than its effect on osteoblasts, and is complicated by a possible effect of fluoride-induced secondary hyperparathyroidism.”
SOURCE: Chachra D, et al. (1999). The effect of fluoride treatment on bone mineral in rabbits. Calcified Tissue International 64:345-351.

“The toxic effects of fluoride were more severe and more complex and the incidence of metabolic bone disease (rickets, osteoporosis, parathyroid hormone bone disease) and bony leg deformities was greater (>90%) in children with calcium deficiency as compared to in children with adequate calcium who largely had osteoslcerotic form of skeletal fluorosis…”
SOURCE: Teotia M, Teotia SP, Singh KP. (1998). Endemic chronic fluoride toxicity and dietary calcium deficiency interaction syndromes of metabolic bone disease and deformities in India: year 2000. Indian Journal of Pediatrics 65:371-81.

“Although some authors have suggested that the resorption observed in skeletal fluorosis is due to secondary hyperparathyroidism in humans and in fluoride-treated animals, others have found no effect of fluoride on parathyroid mass or serum parathyroid levels in animal studies.”
SOURCE: Lundy MW, et al. (1995). Histomophometric analysis of iliac crest bone biopsies in placebo-treated versus fluoride-treated subjects. Osteoporosis International 5:115-129.

“Secondary hyperparathyroidism has been suggested as a possible mechanism by which fluoride produces changes in bone, and hyperparathyroidism has been found in some humans and experimental animals exposed to fluoride. The experimental pigs examined in the present study, however, showed no signs of hyperparathyroidism.”
SOURCE: Kragstrup J, et al. (1989). Effects of fluoride on cortical bone remodeling in the growing domestic pig. Bone 10:421-424.

“A combination of osteosclerosis, osteomalacia and osteoporosis of varying degrees as well as exostoses formation characterzes the bone lesions (of skeletal fluorosis). In a proportion of cases secondary hyperparathyroidism is observed with associated characteristic bone changes.”
SOURCE: Krishnamachari KA. (1986). Skeletal fluorosis in humans: a review of recent progress in the understanding of the disease. Progress in Food and Nutrition Sciences 10(3-4):279-314.

“Fluoride, by the nature of its incorporation into bone crystals and by its direct cytotoxic effect on bone resorbing cells, reduces the availability of calcium from bone. It appears that fluoride ingestion during lactation created a heightened state of calcium homeostatic stress. As a result, bone mineral was mobilized by resorption of the endosteal surface and by cavitation of the interior of the cortex. Secondary hyperparathyroidism is thought to play an integral part (in skeletal fluorosis) in an attempt to maintain calcium homeostasis.”
SOURCE: Ream LJ, et al. (1983). Fluoride ingestion during multiple pregnancies and lactations: microscopic observations on bone of the rat. Virchows Arch [Cell Pathol] 44: 35-44.

“The inhibition of resorptive function together with the decreased level at which bone and serum calcium equilibrate after the incorporation of fluoride would lead to a fall in serum calcium and a compensatory increase in parathyroid hormone secretion. This rise in serum parathyroid hormone would stimulate the differentiation of progenitor cells into both osteoblasts and osteoclasts.”
SOURCE: Ream LJ. (1983). Scanning electron microscopy of the rat femur after fluoride ingestion. Fluoride 16: 169-174.

“The mechanism leading to the hyperfunction of the parathyroid glands in skeletal fluorosis is not clear. Studies on growing rabbits have suggested that fluoride, probably by producing a more stable fluorapatite, reduced the resorption of the fluoride containing bone with a resultant increase in the resorption of normal non-fluoride containing bone and that the hyperfunction of the parathyroids is, therefore, a compensatory mechanism which, probably, develops to maintain the plasma calcium and to overcome the physical effects of the more stable and less reactive fluoroapatite crystals. Jowsey et al (1972) argue that the secondary hyperparathyroidism seen in fluorosis is due to the fact that fluoride directly stimulates osteoblastic activity and that the calcium intake is insufficient to mineralise the rapidly forming new bone tissue. They cite evidence for this from the report of a decreased incidence of radiologically-recognised endemic fluorosis in areas with a high calcium content in the drinking water. More significantly, Jowsey and her co-workers (1972) have found that by combining vitamin D and calcium supplements with fluoride they were able to stimulate bone growth in osteoporotic patients wtihout producing a, concomitant, increase in bone resorption.”
SOURCE: Faccini JM, Teotia SPS. (1974). Histopathological assessment of endemic skeletal fluorosis. Calcified Tissue Research 16: 45-57.

“the increased production of (parathyroid hormone) is strongly suggested by the marked increase in the number of trabecular resorption surfaces and the pattern of tunnelling resorption observed.”
SOURCE: Faccini JM, Teotia SPS. (1974). Histopathological assessment of endemic skeletal fluorosis. Calcified Tissue Research 16: 45-57.

“Fluoride administration in both man and animals has been shown to stimulate new bone formation. However, the bone is poorly mineralized, and osteomalacia and secondary hyperparathyroidism frequently occur.”
SOURCE: Jowsey J, et al. (1972). Effect of combined therapy with sodium fluoride, vitamin D and calcium in osteoporosis. The American Journal of Medicine 53: 43-49.

“[T]here are a number of similarities between the effects of excess parathyroid hormone and the administration of fluoride on bone… In the present study secondary hyperparathyroidism would be a reasonable explanation for the observed increase in endosteal bone resorption, endosteal resorbing surface, and the linear rate of bone resorption (in the fluorotic animals).”
SOURCE: Baylink D, et al. (1970). Effects of fluoride on bone formation, mineralization, and resorption in the rat. In: TL Vischer, ed. (1970). Fluoride in Medicine. Hans Huber, Bern. pp. 37-69.

“The frequent description in the literature of large resorption cavities with fibrous tissue replacement suggested to me that the parathryoids were overactive in skeletal fluorosis, and this was demonstrated by an electron-microscopic study of the parathyroid glands from fluorotic sheep and a concomitant immunoassay of the amount of circulating parathyroid hormone, which was found to be as much as five times higher than resting levels and control levels.”
SOURCE: Faccini JM. (1969). Fluoride and bone. Calcified Tissue Research 3:1-16.

“The demonstrable hyperactivity of the parathyroid glands in fluorotic rabbits and sheep in the presence of this inhibition of resorption suggests that it is a compensatory phenomenon to maintain the serum calcium at a constant level.”
SOURCE: Faccini JM. (1969). Fluoride and bone. Calcified Tissue Research 3:1-16.

“Osteosclerosis from chronic renal disease associated with secondary hyperparathyroidism may produce similar changes (as skeletal fluorosis), and indeed may have intensified the findings (of fluorosis) in one of our patients.”
SOURCE: Morris JW. (1965). Skeletal fluorosis among indians of the American Southwest. American Journal of Roentgenology, Radium Therapy & Nuclear Medicine 94: 608-615.

“While some authors consider the (fluorosis) lesion to be a form of osteosclerosis, others attribute it to mineral deficiency characterized by an increase of osteoid formation. Some consider the osseous condition a response to parathyroid hyperfunction or intoxication; others have reported the aggravating effects of a calcium deficient diet. Studying young dogs, Kellner reported a gross similarity between the bony changes in fluorosis and rickets.”
SOURCE: Belanger LF, et al. (1958). Rachitomimetic effects of fluoride feeding on the skeletal tissues of growing pigs. American Journal of Pathology 34: 25-36.